Bacterial cell culture processes have been developed for the growth of single cell bacteria, yeast and molds which can be characterized as encased with a tough cell wall. Large scale culture of bacterial type cells is highly developed and such culture techniques are less demanding and are not as difficult to cultivate as mammalian cells. Bacterial cells can be grown in large volumes of liquid medium and can be vigorously agitated without any significant damage.
Mammalian cell culture and tissue generation, however, is much more complex because such cells are more delicate and have a more complex nutrient requirement for development. Mammalian cells cannot withstand excessive turbulent action without damage to the cells and must be provided with a complex nutrient medium to support growth. Therefore, bioreactors with internal moving parts or obstructions will subject mammalian cells to high fluid shearing forces that will damage the cells. In addition, bioreactors that utilize mechanical parts, air or fluid movement as a lift mechanism to achieve particle suspension will likewise cause damage to growing cells and tissues due to fluid shear.
A primary use of bioreactors is in research where large numbers of cells are grown to refine the minute quantities of an active material (e.g. proteins) that the cells might secrete. Another use of bioreactors is the scale-up of laboratory cell culture processes for commercial purposes to mass produce the active proteins made by genetically engineered cells and tissues. Because of the need to culture mammalian cells in the laboratory in large quantities, bioreactors and culturing vessels have become an important tool in research and production of cells that produce active proteins.
A current problem in tissue culturing technology is the unavailability of an effective bioreactor for the in vitro cultivation of cells and explants that allows easy access to the materials contained in the vessel. Several devices presently on the market have been used with only limited success since each has limitations which restrict usefulness and versatility. Further, no bioreactor or culture vessel is known that will allow for the unimpeded growth of three dimensional cellular aggregates or tissues.
Cell culturing devices range upward in complexity from the petri dish to sophisticated computer controlled bioreactors. In the past, manufacturers have promoted various technologies to culture cells in the laboratory. For instance, simple adaptations of fermentors or stirred tanks used for the culture of bacteria, were marketed previously as the answer to culturing delicate mammalian cells. One of the principal factors limiting the performance of these systems is their inability to minimize turbulence due to stirring, i.e., shear due to fluid flow, and hence preventing free form association of cells in three dimensions.